Adverse effects on reproductive capacity can occur at every phase of the reproductive process from prenatal development, puberty, to time when conception is occurring and the pregnancy is developing. This research project includes several aspects of the reproductive process, but mostly focuses on factors affecting the ability to conceive and maintain the pregnancy through its first few weeks. The complex biological processes involved include gamete development and maturation, sperm transport through the female reproductive tract, fertilization, early development of the conceptus, implantation, and maintenance of the developing embryo/trophoblast. We have developed methods to estimate environmental effects on fecundability, defined as the per menstrual cycle probability of conceiving, and we have followed women with daily urinary hormone measurements through their pregnancy attempts and early pregnancies. The biological underpinnings of fertility can also influence general health, and we have considered the health effects of female hormones within the framework of this project[unreadable] [unreadable] 1.Data from the Early Pregnancy Study (A.Wilcox, PI) provide a resource for ongoing research into reproductive hormones, fertility, & early pregnancy. This study enrolled women at the time they stopped using birth control in order to conceive & followed them through their 8th week of pregnancy. They collected daily first morning urine specimens & these were analyzed for human chorionic gonadotropin & estrogen and progesterone metabolites. Women with known fertility problems were excluded, so the sample represents normal unassisted reproduction. We have completed analyses of follicular phase length in the Early Pregnancy Study data, & we find longer follicular phases among women who reported using marijuana. This is biologically plausible given the research showing effects on LH secretion & ovulation. We are also examining variation in menstrual bleeding. The pattern of early rise of hCG was also examined for pregnancies that persist beyong menstrual week 6. We found little variation by sex of baby, but a late implantation was associated with a slower rise.[unreadable] 2.We conducted a pilot study to test the stability of hormones in urines stored from the Early Pregnancy Study. We collected a sample of new daily urine specimens during early pregnancy to serve as a reference to evaluate the quality of the stored samples. Estrogen and progesterone metabolite as well as hCG measurements from a sample of the stored urines will be compared to these hormones measured in newly collected urine samples. We enrolled 44 women, 26 of whom became pregnant and collected daily first morning urine specimens. Urine samples from the new collection and stored EPS samples are being analyzed for estrogen and progesterone metabolites as well as for hCG by Jim Kesner at NIOSH.[unreadable] [unreadable] 3..A subsample of urine specimens from the EPS have also been analyzed for phthalates, bisphenol A, and cortisol to see if those analytes can be evaluated in these stored samples. Analysis shows similar distributions of these toxicants as reported for more recently-collected samples and similar within-woman reproducibility measures. This supports analyisis of specimens from the complete EPS study in order to examine the relationship between these exposures and fertility and early pregnancy. [unreadable] [unreadable] 4. There is methodologic interest in quality of self-reported reproductive data, and there have been several efforts to evaluate the validity of such reports. We are evaluating the validity of self-reported cycle characteristics by comparing interview data to prospective daily recording of menstrual bleeding. In another methodologic project, we are using available data to determine how well women can report the timing of their positive pregnancy test. Bias arises in spontaneous abortion & time-to-pregnancy studies when comparing exposed and unexposed groups that differ in timing of pregnancy testing. Those who tend to have delayed pregnancy testing will recognize fewer spontaneous abortions, & they will have longer times to pregnancy. [unreadable] [unreadable] 5. Using data from the Agricultural Health Study, we found that men with high BMI are more likely to be infertile than men of normal weight for height. We replicated those findings in a Norwegian population where data were also were collected on frequency of intercourse. With these additional data we demonstrated that the lower fertility among men with higher BMI does not appear to be explained by them having less sex. [unreadable] 6. Organochlorines accumulate in tissue so that a single measure may be useful as a surrogate for years of exposure. We evaluated change in DDE and PCB levels in reproductive age women and the factors that affect the rates of change. There was a strong correlation between measurements over twenty years apart for both toxicants, and data on breast feeding, initial BMI, and weight gain allowed for further predictive precision.